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Regulation of Matrix Metalloproteinase-9 (MMP-9) by Translational Efficiency in Murine Prostate Carcinoma Cells¹

Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104

Expression of increased levels of matrix metalloproteinase-9 (MMP-9) hasbeen implicated in tumor progression and angiogenesis. Much of our knowledge of the controls of MMP-9 levels has focused on transcription. Here we show that MMP-9 levels are also controlled by translational efficiency in murine prostate carcinoma cells. The murine prostate carcinoma cells 148-1,LMD and 148-1,PA were derived from a single mouse that had been implanted with urogenital sinus transformed by ras and myc. 148-1,PA secretes little MMP-9 yet has equivalent amounts of MMP-9 mRNA as the cell line 148-1,LMD that secretes substantially more. Infection with a retroviral vector for murine MMP-9 led to more expression of MMP-9 in both cases, but the differential remained. Human MMP-9 is equally expressed in both cells after infection with a vector for human MMP-9 indicating that the effect is species-specific. Pulse chase analysis revealed that MMP-9 was synthesized more rapidly in the 148-1,LMD cells than in the 148-1,PA cells. Markedly more MMP-9 mRNA was associated with polysomes in the cell line synthesizing more MMP-9. These results indicate regulation of MMP-9 synthesis at the level of translational efficiency.

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